title: Female neuregulin 1 heterozygous mice require repeated exposure to Δ⁹-tetrahydrocannabinol to alter sensorimotor gating function.
abstract: BACKGROUND
  The schizophrenia susceptibility gene neuregulin 1 (NRG1) confers vulnerability to the neurobehavioural eff ects of cannabinoids differently across sexes. Male but not female Nrg1 heterozygous (HET) mice display facilitation of prepulse inhibition (PPI) to acute Δ⁹-tetrahydrocannabinol (THC) exposure compared to WT controls. We aim to observe whether repeated administration of THC may overcome the acute insensitivity of female Nrg1 HET mice to THC exposure.
  
  
  METHODS
  Female Nrg1 HET mice and WT controls were administered THC daily for 21 days, with PPI and anxiety-related behaviour in the light-dark test (LD) examined on the fi rst and last day of treatment and 21 days after cessation of dosing.
  
  
  RESULTS
  Following repeated, but not acute THC exposure, female Nrg1 HET mice displayed THC-induced facilitation of PPI which was not observed in WT mice treated with THC. There were no residual eff ects of THC on PPI in either genotype when assessed 21 days following the final THC dose. An anxiogenic response to THC was evident following repeated, but not acute, administration in the LD test in both genotypes.
  
  
  CONCLUSIONS
  These findings show that the acute insensitivity of female Nrg1 HET mice to THC-induced PPI facilitation may be overcome following repeated THC exposure.
authors.affiliation: Discipline of Pharmacology, University of Sydney, Sydney, NSW, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Spencer
authors.forename: T W
authors.initials: TW
authors.lastname: Chohan
authors.forename: T
authors.initials: T
authors.lastname: Karl
authors.forename: J C
authors.initials: JC
authors.lastname: Arnold
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D051379:Mice; D020890:Neuregulin-1 / Q000235:genetics*; D055139:Sensory Gating / Q000187:drug effects* / Q000235:genetics*
chemical_list: D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D013759:Dronabinol